The drug is a potent dual reuptake inhibitor of serotonin andnorepinephrine and possesses comparable affinities in binding to both transport sites. The drug lacks affinity for monoamine receptors within the central nervous system, however. While there is some data regarding the pharmacokinetic profile of duloxetine in humans, its half-life is reportedly 10 to 15 hours.
Cymbalta has also received FDA approval for the treatment of diabetic neuropathy.
Antidepressant, dual-reuptake inhibitor
The exact mechanism of action of duloxetine is unknown in humans, the drug’s antidepressant and pain inhibitory actions are believed to be linked to its potentiation of serotonergic or noradrenergic activity in the central nervous system.
Preclinical trials have shown that duloxetine is a potent inhibitor of neuronal serotonin and norepinephrine but a less potent inhibitor of dopamine reuptake. Duloxetine is extensively metabolized, but the major metabolites in circulation have not been shown to substantially contribute to the drug’s pharmacologic activity.
Indications and Dosage:
Cymbalta is indicated for the treatment of major depressive disorder (MDD).
The drug’s efficacy has been established in 8- or 9-week placebo-controlled trials of outpatients meeting DSM-IV diagnostic criteria for MDD. A major depressive episode implies a prominent and relatively persistent depressed or dysphoric mood that normally interferes with the person’s daily functioning, and includes at least 5 of the following 9 symptoms: depressed mood, significant change in weight and/or appetite, alteration of psychomotor functions, loss of interest in normal activities, feelings of worthlessness or guilt, insomnia or hypersomnia, increased fatigue, slowed thinking or difficulty concentrating, or a suicide attempt or suicidal ideation. The efficacy of Cymbalta on hospitalized patients with MDD has not been studied.
As well, the effectiveness of Cymbalta in long-term use for MDD (more than 9 weeks) has not been systematically evaluated in controlled studies. The prescribing physician choosing to administer Cymbalta for long-term use should periodically assess the long-term efficacy of the drug for the patient.
However, Nardil should rarely be the first antidepressant tried. It proves more suitable for use with people who have failed to respond to more common drugs associated with these conditions.
Duloxetine is also indicated for the management of neuropathic pain associated with diabetic peripheral neuropathy.
For MDD, the initial dose of Cymbalta should be administered at a total dosage of 40 to 60mg/day, with or without food. There is no evidence that doses beyond 60mg/day have any additional benefit.
For Diabetic Peripheral Neuropathic Pain (DPNP) Cymbalta should be given at a total dose of 60mg/day, once a day with or without food.
While a 120mg/day dose was shown effective and safe, there is no evidence that doses higher than 60mg/day add any benefit, and tolerance to the higher dose is clearly less. For individuals concerned with tolerability, a lower initial dose may be necessary. Since diabetes is frequently complicated by renal disease, a lower starting dose and gradual increase in dosage should be taken into consideration for those persons with renal impairment.
Generally, it is agreed that acute episode of major depression require several months or longer of sustained pharmacologic therapy. There is insufficient evidence available to answer the question of how long a patient should continue to be treated with Cymbalta. Individuals taking Cymbalta should be periodically reassessed to determine the need for maintenance treatment.
The progression of diabetic peripheral neuropathy is extremely variable, and as such, managing the pain is empirical and the efficacy of Cymbalta must be assessed on an individual basis. Effectiveness beyond 12 weeks has not been systematically studied in placebo-controlled trials, but a one-year open-label safety study was conducted.
The most common side effects of duloxetine treatment include nausea, dry mouth and somnolence (drowsiness). Other symptoms such as fatigue, dizziness, decreased appetite, increased sweating, vomiting, muscle cramps, cough, diarrhea, decrease in weight, tremor, hot flushes, blurred vision, constipation, decreased libido, anorgasmia, and erectile dysfunction and difficult or delayed ejaculation in men were reported.
Adverse interactions may occur with the use of Cymbalta in conjunction with alcohol, CNS-acting drugs (including those having a similar mechanism of action), and drugs that affect gastric acidity.
Information for Parents and Kids:
Children and adolescents taking antidepressants may experience increased suicidal thoughts or actions. Though the drug is prescribed for children, the FDA has not approved it for use in children. Anyone considering administering Cymbalta or other antidepressants to children or adolescents should carefully balance the risk with the clinical need. Child or adolescent patients should be monitored closely, especially in the initial phase of treatment and at any time of a change in dosage (increase or decrease). Any signs of worsening depression symptoms, suicidal thought or action, or unusual changes in behavior should be promptly reported to a physician. Cymbalta is not approved for use in and should not be administered to anyone under the age of 18.
Warnings and Precautions:
Individuals taking Cymbalta should watch for any change in symptoms or any new ones that appear abruptly, especially suicidal behavior or thoughts, agitation, psychomotor restlessness, hypomania, mania, anxiety, panic attacks, insomnia, irritability, aggressiveness, hostility, impulsivity, worsening depression, unusual changes in behavior, and report them to a doctor immediately. It’s very important to be especially observant in the beginning stages of treatment and whenever there is a change in dosage for anyone taking this or any antidepressant.
Blood pressure should be measured prior to initiating treatment and periodically measured throughout treatment.
Cymbalta has not been systematically evaluated in patients with a seizure disorder, and such patients were excluded from clinical studies. In placebo-controlled clinical studies in patients with MDD, seizures occurred in 0.1% (1/1139) of patients treated with duloxetine and 0% (0/777) of placebo patients. In similar trials in patients with diabetic peripheral neuropathy, seizures did not occur in any patients treated with either Cymbalta or placebo. Cymbalta should be administered carefully in persons with a history of seizure disorder.
Duloxetine should be given cautiously to patients with controlled narrow-angle glaucoma.
Abrupt discontinuation of Cymbalta is not recommended, as withdrawal symptoms may be experienced.
Withdrawal symptoms associated with Cymbalta include dizziness, nausea, headache, paresthesia, vomiting, irritability, nightmares, agitation, sensory disturbance, confusion, insomnia, lethargy, seizures, tinnitus and hypomania.
Over-dosage & Contraindications:
There is limited clinical experience with Cymbalta overdose in humans. In clinical trials as of October 2003, no cases of fatal acute overdose have been reported. Four non-fatal acute ingestions of the drug, alone or in conjunction with other drugs, were reported.
There is no known specific antidote to Cymbalta. In case of acute overdose, treatment should consist of measures common with overdose of any drug.
Cymbalta is contraindicated in persons with a known hypersensitivity to duloxetine or any of its active ingredients.
People taking MAOIs should not take Cymbalta. Individuals with uncontrolled narrow-angle glaucoma had an increased risk of mydriasis (prolonged abnormal dilation of the pupil) and should avoid treatment with Cymbalta.
Generic Name: duloxetine
Chemical Formula: C18H19NOS, HCl
Routes of Administration: oral
Elimination Half Life: 8-17 hours
Legal Status: by prescription only